Effects of KCa3.1 blockade on DADs and DAD-induced triggered activity
To determine whether the influence of burst pacing was site-specific, we applied the protocol of pacing at CL of 1000ms through the electrodes located at the PVs, SVC, LA, and RA. After super-fusion with isoproterenol (1μM) and high calcium (5.4mM), the Delayed afterdepolarization (DAD) and DAD-induced triggered activity was induced with the pacing CL of 500ms, 300ms, 200ms in PVs and SVC, but not in the RA and LA. Interestingly, after TRAM-34 (5uM) administration, DAD-induced triggered activity was inhibited significantly in the PVs and SVC.
Figure 1A shows a representative example of the effect of TRAM-34 on DADs and DAD-induced triggered activity in a rabbit PV. Under high calcium (5.4mM) and isoproterenol (1uM) induced DADs and DAD-induced triggered activity following 20 beats of BCLs of 500, 300, and 200ms in PV preparations. Figure 1B shows the incidence of DAD-induced trigger activity in thoracic veins and atrium. The incidences of DAD-induced trigger activity were 6 of 6 (100%), 4 of 6 (66.7%), 0 of 6 (0%) in PVs, SVC, and atrium in high calcium and isoproterenol respectively. After 5nM TRAM-34 super-fused, none of the DAD-induced triggered activity was shown. The DAD-triggered activity was more easily induced in PVs and SVC than atrium.